Zirconium-Catalyzed Hydroaminoalkylation of Alkynes for the Synthesis of Allylic Amines

Abstract

A zirconium-catalyzed hydroaminoalkylation of alkynes to access α,β,γ-substituted allylic amines in an atomeconomic fashion is reported. The reaction is compatible with N-(trimethylsilyl)benzylamine and a variety of N-benzylaniline substrates, with the latter giving the allylic amine as the sole organic product. Various internal alkynes with electron-withdrawing and electron-donating substituents were tolerated. Model intermediates of the reaction were synthesized and structurally characterized. Stoichiometric studies on key intermediates revealed that the open coordination sphere at zirconium, imparted by the tethered bis(ureate) ligand, is crucial for the coordination of neutral donors. These complexes may serve as models for the inner-sphere protonolysis reactions required for catalytic turnover.

Zirconium Catalyzed Hydroaminoalkylation for the Synthesis of α‐Arylated Amines and N‐Heterocycles

“…Notably, N ‐benzylaniline has been reported to undergo zirconium mediated reactivity with alkynes to generate chiral allylamines, at the expense of stoichiometric zirconium [17] . Both N ‐silylamines and N ‐benzylanilines have also been shown to be compatible with zirconium catalyzed HAA of alkynes to deliver allylamines by our group [18] . As previously observed, [14] linear regioselectivity is favored with sterically demanding and electronically biased vinysilanes.…”

Ni-Catalyzed Hydroaminoalkylation of Alkynes with Amines

“…1b). 42 The bulky ligand proved critical to the reactivity, not only facilitating alkyne insertion, but also allowing the coordination of neutral amines to the metal center for subsequent easier protonolysis. Despite this big advance, the early transition metal Zr-catalyzed method still suffered from some undesired limitations such as unavoidable hydroamination side reaction in many cases, di cult-to-remove N-aryl protecting groups, and tricky regioselectivity under relatively harsh conditions.…”

Ni-catalyzed hydroaminoalkylation of alkynes with amines

“…Most recently, during our submission, Schafer group used a tetradentate bis(ureate) ligand and metal Zr to in situ form a bulky Zr catalyst, achieving a catalytic hydroaminoalkylation of alkynes for the first time (Fig. 1b) 40,41 . The bulky ligand proved critical to the reactivity, not only facilitating alkyne insertion, but also allowing the coordination of neutral amines to the metal center for subsequent easier protonolysis.…”